beta2- and beta3-Adrenoceptor polymorphisms relate to subsequent weight gain and blood pressure elevation in obese normotensive individuals.

High blood pressure (BP) is a major determinant of cardiovascular events in obesity. The beta2- and beta3-adrenoceptor polymorphisms are associated with obesity and hypertension. In the present study, we examine the relationships of beta2- and beta3-adrenoceptor polymorphisms with further weight gain-induced BP elevation in obese subjects. Changes in BP, body weight, total body fat-mass, waist-to-hip ratio, plasma norepinephrine (NE) and leptin levels, and beta2(Arg16Gly)- and beta3(Trp64Arg)-adrenoceptor polymorphisms were measured periodically over a 5-year period in 55 entry obese (body mass index [BMI]> or =25.0 kg/m(2)) normotensive (BP<140/90 mmHg) men. BP elevation and weight gain were defined as > or =10% increases from entry levels over 5 years in mean BP or BMI. Obese subjects with weight gain, BP elevation or weight gain-induced BP elevation had higher frequencies of the Gly16 allele of Arg16GIy and Arg64 allele of Trp64Arg. Subjects carrying the Gly16 or Arg64 alleles had significantly greater total fat-mass and waist-to-hip ratio at entry and over a 5-year period compared to the subjects who did not carry these polymorphisms. Subjects carrying the Gly16 allele had similar levels of plasma NE, higher levels of plasma leptin and a lower slope of the regression lines between plasma leptin and NE levels. Those carrying the Arg64 allele had higher plasma NE levels at entry and over a 5-year period compared to the subjects without the Arg64 allele, but plasma leptin levels and slopes were similar. The findings demonstrate that the Arg64 allele of the beta3-adrenoceptor polymorphisms relates to weight gain-induced BP elevation accompanying high plasma NE (heightened sympathetic activity) in obese men. The Gly16 allele of the beta2-adrenoceptor polymorphisms links to weight gain-induced BP elevation associated with leptin resistance. beta2- and beta3-adrenoceptor polymorphisms could predict the future BP elevation and further weight gain-induced BP elevation in originally obese subjects.     

Estimation of base blood pressure by using a new device in the outpatient clinic.

Direct measurement of intra-arterial blood pressure (BP) for 24-h provides approximately 100,000 values that vary enormously, but each (BPi) can be expressed by the equation BPi = BP0 + DeltaBPi (BP0, base BP; DeltaBPi, BP increment, i=1, 2, ..., 100 x 10(3)). About 20% of outpatients with hypertension exhibit white-coat hypertension (WCH). In such patients, DeltaBPc (i = c; c, time at the clinic) is surmised to be large. A method for explaining the physiological factors in DeltaBPc and the estimation of base BP in the outpatient clinic is important. This study addresses this issue. A total of 293 subjects were divided into four groups: 1) WCH group, 45 individuals (office BP > or = 140/90 mmHg and 24-h indirect BP < 125/80 mmHg); 2) normotensive (NT) group, 84 controls matched for age and sex; 3) WHO-I group, 95 hypertensive patients with WHO stage I (office BP > or = 140/90 mmHg and 24-h BP > or = 125/80 mmHg); and 4) WHO-II group, 69 hypertensive patients with WHO stage II. Their BPc and heart rate (HR; HRc, clinic HR) values were measured by a BP-ECG monitoring device in the outpatient clinic. Power-spectral analysis was used to obtain the ratio between the low-frequency component (LF) and high-frequency component (HF) of ECG-RR variability (LF/HF = LH). Twenty-four-hour indirect BP (and BP0) and base HR (HR0) were measured by a portable device (TM2425) at 30-min intervals. Then, DeltaBPc (= BPc - BP0) was estimated by performing linear multivariate analysis applying the model equation DeltaBPc = (BPc -alphaLH)(1-betaHR0/HRc) + epsilon to the above variables (alpha and beta, constant values; epsilon, error). This model equation made it possible to estimate BP0 (and DeltaBPc) with a high coefficient of correlation (r > or = 0.85, mean of error less than 0.82 +/- 5.9 mmHg). The predictive accuracy for discrimination between WCH and sustained hypertension (WHO-I and WHO-II groups) by this equation was 88%. The new DeltaBP-estimation device (BP-ECG monitor) enabled us to infer BP0 and is therefore useful in estimating WCH in the outpatient clinic.     

A case of parathyroid hormone-related peptide producing gallbladder carcinoma presenting humoral hypercalcemia of malignancy]

Humoral hypercalcemia of malignancy (HHM) in neoplastic syndrome has been most commonly reported in squamous cell carcinoma. Gallbladder carcinoma with HHM is uncommon. In this report, we describe a male case of gallbladder carcinoma with marked hypercalcemia and a high level of serum parathyroid hormone-related peptide (PTHrP). An immunohistochemical examination using PTHrP was also positive.     

Distinct osteogenic mechanisms of bones of distinct origins

Mammalian bones have three distinct origins (paraxial mesoderm, lateral plate mesoderm, and neural crest) and undergo two different modes of formation (intra-membranous and endochondral). Bones derived from the paraxial mesoderm and lateral plate mesoderm mainly form through the endochondral process. During this process, hypertrophic chondrocytes play a vital role in inducing both osteogenesis and angiogenesis. One of the essential osteogenic factors secreted from hypertrophic chondrocytes is Indian hedgehog (Ihh). In contrast, bones derived from the neural crest mainly form through the intramembranous pro-cess and do not require Ihh. Thus, depending on their origin, bones have distinct signaling properties, which need to be considered in the research and application of bone biology.Presented at the 18th Annual Research Meeting of the Japanese Orthopaedic Association, Kitakyushu, Japan, October 17, 2003     

Epinephrine is an enhancer of rat intestinal absorption.

Some physiological substances, including acetylcholine and nitric oxide, are useful candidates for stimulation of intestinal absorption of drugs. In the present study, we elucidated the ability of epinephrine (Epi) to stimulate the intestinal absorption of drugs. We evaluated the ability of Epi to enhance absorption of macromolecules using dextran (Mw 4000 Da), which is poorly absorbed from the intestine, as a model compound in situ in a closed loop of the rat jejunum. Treatment of the jejunum with Epi resulted in significant increase in absorption of dextran in a dose-dependent fashion. The area under the curve (AUC) from 0 to 4 h in the Epi-treated jejunum was 13-fold higher than that in the vehicle-treated jejunum. The absorption-enhancing activity of Epi was 40-fold higher than that of caprate, a clinically used absorption-enhancer of drugs. In the experimental conditions used in this study, histological injury of the mucosa and perturbation of the mucosal membrane were not observed in the Epi-treated jejunum. Treatment with an antagonist of alpha-adrenergic receptors attenuated the stimulation of intestinal absorption by Epi, and treatment with an agonist of alpha-adrenergic receptors resulted in enhancement of intestinal absorption. While an antagonist of beta-adrenergic receptors enhanced the absorption-enhancing effect of Epi, an agonist of beta-adrenergic receptors stimulated intestinal absorption. These results indicate that stimulation of adrenergic receptors may be a novel strategy for intestinal absorption of drugs.     

ENDOSCOPIC OBSERVATION OF MUCOSAL SPREAD LESION OF CHOLANGIOCARCINOMA USING PERORAL CHOLANGIOSCOPY WITH NARROW BAND IMAGING

A 69‐year‐old man was admitted to Toho University Omori Medical Center complaining of icterus. Abdominal computed tomography, magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography were suspicious of cholangioma of inferior bile duct. Peroral cholangioscopy using narrow band imaging (NBI) was performed and it was possible to diagnose the mucosal spread lesions of cholangioma. Histological findings reflected the endoscopic findings. Mucosal spread lesions of cholangiocarcinoma were successfully diagnosed using the CHF‐B260 for NBI.     

Surgical treatment for coronary artery aneurysm

Two successful cases of the surgical treatment for coronary artery aneurysm (non-Kawasaki disease) were reported. The first case had a saccular aneurysm on the left circumflex coronary artery (LCx) #14. Resection of the LCx aneurysm was performed subsequent to single vessel coronary artery bypass grafting (CABG) to the distal portion of LCx#14 under the cardioplegic cardiac arrest. The second case had aneurysms on both the left anterior descending artery (LAD) #7 (fusiform) and the LCx#11 (saccular). After double vessel CABG to LAD#7 and LCx#11, ligation or resection of two aneurysms was performed successfully. Postoperative courses have been uneventful with good angiographic results achieved. Since these surgical procedures demonstrated safety, the patients are expected to achieve a good long-term prognosis.